Can Fractional Urea Excretion Be A Marker in Pediatric Urinary Stone Disease?

Abstract

Introduction: In the setting of pediatric urolithiasis, it is important to determine the presence of any metabolic disorder to prevent new stone formation and to treat the existing stone. With this aim, the urinary excretions of electrolytes and uric acid are usually obtained. Fractional excretion of urea (FeU) has been demonstrated to be useful in the setting of acute renal injury. However it has not been studied in the setting of pediatric stone disease. The objective of this study is to search the importance of FeU in pediatric stone disease and to compare FeU with other urine electrolyte excretions and uric acid excretion. Materials and Methods: We retrospectively evaluated the laboratory and medical records of 41 pediatric urolithiasis patients whose FeU percentages were studied together with the etiologic work-up. Patients were divided into two groups as microlithiasis and macrolithiasis. Demographic and laboratory data as well as FeU were compared between the two groups. Results: Twenty-four patients (59%) had stone size less than 3 mms, seventeen patients (41%) had stones larger than 5 mms. Among all patients 20 of them were boys, 21 of them were girls. M/F ratio was 13/11 in microlithiasis and 7/10 in macrolithiasis group. Mean age was 55.8 months in microlithiasis group, wheras 39 months in macrolithiasis group. Mean serum urea, creatinine, sodium, potassium, phosphorus levels and FeNa, FeU and TRP percentages were similar between the two groups. (p>0.05). We divided the patients according to their FeU percentages as FeU<35% and FeU ≥35%, and compared the microlithiasis and macrolithiasis groups. Among 24 patients with microlithiasis, 20 patients had FeU greater than 35%, and 4 patient had FeU less than 35%. To differentiate microlithiasis from macrolithiasis the sensitivity and spesificity of FeU≥35 is 83% and 6% respectively. For FeU<35%, sensitivity and spesificity of the test to differentiate microlithiasis from macrolithiasis is 17% and 94% respectively (p>0.05). When we analyze FeNa, among the two groups, For FeNa<1%, sensitivity and spesificity of the test to differentiate microlithiasis from macrolithiasis is 53% and 25% respectively. And for FeNa ≥1% the sensitivity and the spesificity of the test is 47% and 75% respectively. (p>0.05). The urinary calcium excretion of the patients (random urine calcium/creatinine ratios) are correlated with random urine uric acid/creatinine ratios in both microlithiasis and macrolithiasis groups (p=0.001). Random urine calcium/creatinine ratio also correlates with the tubular phosphorus reabsorption (p=0.023), as well as random urine uric acid excretion correlates with tubular phosphorus reabsorption (p=0.024). Conclusion: Fractional excretion of urea is not affected from the size of the stone. However, urinary urea excretion is associated with urinary sodium and uric acid excretion. Further studies with larger groups and comparison of the urolithiasis patients with healthy children without urinary stones in the controlled studies will reveal the exact results.

Keywords

• urea excretion
• nephrolithiasis
• children

Kaynakça

1. 1.Bowen DK, Tasian GE. Pediatric Stone Disease. Urol Clin North Am. 2018; 45(4):539-50. https://doi.org/10.1016/j.ucl.2018.06.002.
2. 2.Baştuğ F, Ağbaş A, Tülpar S, et al. Comparison of infants and children with urolithiasis: a large case series. Urolithiasis. 2022; 50(4):411-21. https://doi.org/10.1007/s00240-022-01327-0
3. 3.Lopez M, Hoppe B. History, epidemiology and regional diversities of urolithiasis. Pediatr Nephrol. 210; 25:49–59. https://doi.org/10. 1007/ s00467- 008- 0960-5
4. 4.Akinci M, Esen T, Tellaloğlu S. Urinary stone disease in Turkey: an updated epidemiological study. Eur Urol. 1991; 20:200–3. https://doi.org/10.1159/000471700 5.Bak M, Ural R, Agin H, et al. The metabolic etiology of urolithiasis in Turkish children. Int Urol Nephrol. 2009. https://doi.org/10.1007/s11255-008-9513-x
5. 6.Aksoy OY, Aydin Z, Inozu M, et al. Fractional excretion of urea in pediatric patients with acute kidney injury. Turkish J Pediatr Dis. 2023; 17: 91-5. https://doi.org/10.12956/tchd.1036384
6. 7.Fahimi D, Mohajeri S, Hajizadeh N, et al. Comparison between fractional excretions of urea and sodium in children with acute kidney injury. Pediatr Nephrol. 2009; 24: 2409–12. https://doi.org/10.1007/s00467-009-1271-1.
7. 8.Carvounis CP, Nisar S, Guro-Razuman S. Significance of the fractional excretion of urea in the differential diagnosis of acute renal failure. Kidney Int. 2002; 62: 2223–9. https://doi.org/10.1046/j.1523-1755.2002.00683.x.
8. 9.Diskin CJ, Stokes TJ, Dansby LM, et al. Toward the optimal clinical use of the fraction excretion of solutes in oliguric azotemia. Ren Fail. 2010; 32: 1245-54. https://doi.org/10.3109/0886022X.2010.517353.

9. 10.Musch W, Verfaillie L, Decaux G. Age-related increase in plasma urea level and decrease in fractional urea excretion: clinical application in the syndrome of inappropriate secretion of antidiuretic hormone. Clin J Am Soc Nephrol. 2006; 1:909–14. https://doi.org/10.2215/CJN.00320106.
10. 11.Marra G, Taroni F, Berrettini A, et al. Pediatric nephrolithiasis: a systematic approach from diagnosis to treatment. J Nephrol. 2019; 32(2): 199-210. https://doi.org/10.1007/s40620-018-0487-1
11. 12.Weiner ID, Mitch WE, Sands JM. Urea and ammonia metabolism and the control of renal nitrogen excretion. Clin J Am Soc Nephrol. 2015; 10(8): 1444-58. https://doi.org/10.2215/CJN.10311013
12. 13.Kaplan AA, Kohn OF. Fractional excretion of urea as a guide to renal dysfunction. Am J Nephrol. 1992; 12(1-2): 49-54. https://doi.org/10.1159/000168417.
13. 14.Polito C, Signoriello G, Andreoli S, et al. A. Urinary urea excretion in idiopathic hypercalciuria of children. J Pediatr Urol. 2006; 2(5): 419-23. https://doi.org/10.1016/j.jpurol.2005.09.003
14. 15.Polito C, La Manna A, Signoriello G, et al. Differing urinary urea excretion among children with idiopathic hypercalciuria and/or hyperuricosuria. J Pediatr Urol. 2008; 4(1): 55-9. https://doi.org/10.1016/j.jpurol.2007.04.001
15. 16.Kovacević L, Kovacević S, Smoljanić Z, et al. Izlucivanje natrijuma kod dece s litogenim poremećajima [Sodium excretion in children with lithogenic disorders]. Srp Arh Celok Lek. 1998; 126(9-10): 321-26.
16. 17.Humalda JK, Yeung SMH, Geleijnse JM, et al. Effects of potassium or sodium supplementation on mineral homeostasis: a controlled dietary intervention study. J Clin Endocrinol Metab. 2020; 105(9): e3246-56. https://doi.org/10.1210/clinem/dgaa359